| First Author | Johnson C | Year | 2004 |
| Journal | Circ Res | Volume | 94 |
| Issue | 2 | Pages | 262-8 |
| PubMed ID | 14670843 | Mgi Jnum | J:95880 |
| Mgi Id | MGI:3527918 | Doi | 10.1161/01.RES.0000111527.42357.62 |
| Citation | Johnson C, et al. (2004) Matrix metalloproteinase-9 is required for adequate angiogenic revascularization of ischemic tissues: potential role in capillary branching. Circ Res 94(2):262-8 |
| abstractText | Angiogenesis, an essential component of a variety of physiological and pathological processes, offers attractive opportunities for therapeutic regulation. We hypothesized that matrix metalloproteinase-9 genetic deficiency (MMP-9-/-) will impair angiogenesis triggered by tissue ischemia, induced experimentally by femoral artery ligation in mice. To investigate the role of MMP-9, we performed a series of biochemical and histological analyses, including zymography, simultaneous detection of perfused capillaries, MMP-9 promoter activity, MMP-9 protein, and macrophages in MMP-9-/- and wild-type (WT) mice. We found that ischemia resulted in doubling of capillary density in WT and no change in the MMP-9-/- ischemic tissues, which translated into increased (39%) perfusion capacity only in the WT at 14 days after ligation. We also confirmed that capillaries in the MMP-9-/- presented significantly (P<0.05) less points of capillary intersections, interpreted by us as decreased branching. The combined conclusions from simultaneous localizations of MMP-9 expression, capillaries, and macrophages suggested that macrophage MMP-9 participates in capillary branching. Transplantation of WT bone marrow into the MMP-9-/-, restored capillary branching, further supporting the contribution of bone marrow-derived macrophages in supplying the necessary MMP-9. Our study indicates that angiogenesis triggered by tissue ischemia requires MMP-9, which may be involved in capillary branching, a potential novel role for this MMP that could be exploited to control angiogenesis. |
